A single center, open label study assessing the feasibility, safety and therapeutic effect of Minocycline in adult patients with diagnosis of unipolar depression. Up to 30 patients diagnosed with unipolar depression that are in a current depressive episode. The patients will be of all racial, ethnic and gender categories, ranging from 18 to 68 years of age, and have HDRS-21≥20. All subjects will continue to take their treatment with antidepressant medications for the duration of the study. All subjects are prescribed minocycline 200 mg/day orally (2X100 mg) for the first 3 days. than, all subjects are prescribed minocycline 400 mg/day orally (2X200 mg) from day 4 until termination visit (day 35). The primary objective of this study is to assess the therapeutic effect of Minocycline in unipolar depression.

The secondary objectives of this study are to assess the therapeutic effect, the feasibility and safety of Minocycline in unipolar depression.

Inclusion Criteria:

1. Outpatients and inpatients

2. Men and women 18-68 years of age.

3. Primary DSM-IV diagnosis of Depression, single or recurrent episode confirmed by the Structured Clinical Interview for the DSM-IV (SCID-IV), with the additional requirements of a current episode ≥4 weeks and CGI-S ≥4.

4. Total HDRS-21 ≥20 and Item 1 score ≥2 at the screening visit.

5. The patient did not respond to at least one antidepressant medication given for an accepted dose and duration.

6. Capable and willing to provide informed consent

7. Able to adhere to the treatment schedule.

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Exclusion Criteria:

1. Depression secondary to a general medical condition.

2. History of substance abuse or dependence within the past 6 month (except opioids, nicotine and caffeine).

3. All antidepressant medications, must have been in stable dosage for at least 3 weeks prior to entry into the study, with no anticipation of change over the duration of the study.

4. Use of any medication(s) listed on the Excluded medication list within the time that mansion for each medication on the list.

5. Any psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features • Bipolar disorder • Eating disorder

6. Subjects who were taking a known contraindication to minocycline treatment.

7. Subjects who had received treatment with minocycline or β-lactam antibiotics in the preceding half year before study entry.

8. Present suicidal risk as assessed by the investigator or significant suicide risk based on HDRS-21 item 3 score of 3 or 4 or a history of attempted suicide in the last 6 month

9. Known or suspected pregnancy or women of childbearing potential and not using a medically accepted form of contraception when engaging in sexual intercourse.(if using oral contraceptives, during the minocycline treatment, subject should use an additional contraceptives), or women who are breastfeeding

10. Patients with severe hepatic or renal insufficiency.

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